The objective of this project is development of new mass spectral techniques in order to provide innovative and/or more rapid solutions to problems involving (1) chemical structure determination, (2) complex mixture analysis and (3) measurement of trace components in biological systems. Electrospray ionization mass spectrometry (ESI/MS), tandem mass spectrometry (MS/MS), combined liquid chromatography-mass spectrometry (LC/MS) and matrix-assisted laser desorption ionization (MALDI) mass spectrometry are the techniques of current interest. A narrow-bore (2 mm i.d., 0.200 ml/min), reversed-phase liquid chromatography system, whose flow can be automatically diverted for on- line sample desalting, is being employed to develop a rapid method utilizing tandem mass spectrometry for measuring the Phase II anti-AIDS drug 2-b-fluoro-2,3-dideoxyadenosine (lodenosine, F-ddA), its anti-HIV- active deaminated metabolite 2-b-fluoro-2,3-dideoxyinosine (F-ddI) and the companion antiretroviral agent stavudine (2-deoxythymidinene, d4T) in human plasma with high specificity and sensitivity. This methodology is being applied to determine the pharmacokinetics, metabolism and disposition of oral F-ddA during a Phase I clinical trial of this agent in AIDS patients receiving combination antiretroviral therapy. Fast atom bombardment mass spectrometry (FAB/MS) is used to support the LMC synthetic effort through structural characterization of new compounds and synthetic intermediates. Mass spectrometric studies to confirm the structural identity of compounds identified as HIV-1 integrase inhibitors through 3-dimensional database searching are ongoing. FAB liquid matrix reactions involving ion pairing, reduction, dehalogenation and radical cation/anion formation continue to be studied and characterized to ensure the interpretability and reliability of these analyses.AIDS Title: Application of New Mass Spectral Methods for the Analysis of Anti-AIDS Agents - electrospray ionization, liquid chromatography - mass spectrometry, mass spectrometry, pharmacokinetics, tandem mass spectrometry, 2'-beta- fluoro-2',3'-dideoxyadenosine, - Human Tissues, Fluids, Cells, etc.